New domino reaction. One pot synthesis of 4,7-dihydroxythioaurone derivatives from benzaldehydes and 4-acetyl-2-oxo-benz[1,3]oxathiole

Article abstract of DOI:10.1016/j.tet.2005.06.107

A convenient synthesis of 4,7-dihydroxythioaurone derivatives by a one pot reaction of benzaldehydes with 4-acetyl-2-oxo-benz[1,3]oxathioles and piperidine acetate in DMSO is described. The structures of the compounds, including double bond geometry were proved unequivocally by NMR methods. The thioaurone ring system seems to be formed by three consecutive reactions: opening of the oxathiolone ring with piperidine, oxidation of the formed mercapto group with DMSO or/and air to disulfide, and condensation with aldehyde.

Full text of DOI:10.1016/j.tet.2005.06.107

Tetrahedron 61 (2005) 8648–8655
New domino reaction. One pot synthesis of
4,7-dihydroxythioaurone derivatives from benzaldehydes and
4-acetyl-2-oxo-benz[1,3]oxathiole
a
a
b
Marek T. Konieczny,a, Wojciech Konieczny, Stefan Wolniewicz, Konstanty Wierzba,
*
b
Yoshimitsu Suda and Paweł Sowinski
c
´
a
´
´
Department of Organic Chemistry, Medical University of Gdansk, 80-416 Gdansk, Poland
bHanno Research Center, Taiho Pharmaceutical Company, Hanno-city, Saitama 357-8527, Japan
´ ´
Laboratory of Nuclear Magnetic Resonance Spectroscopy, Gdansk University of Technology, 80-952 Gdansk, Poland
c
Received 27 April 2005; revised 13 June 2005; accepted 30 June 2005
Available online 15 July 2005
Abstract—A convenient synthesis of 4,7-dihydroxythioaurone derivatives by a one pot reaction of benzaldehydes with 4-acetyl-2-oxo-
benz[1,3]oxathioles and piperidine acetate in DMSO is described. The structures of the compounds, including double bond geometry were
proved unequivocally by NMR methods. The thioaurone ring system seems to be formed by three consecutive reactions: opening of the
oxathiolone ring with piperidine, oxidation of the formed mercapto group with DMSO or/and air to disulfide, and condensation with
aldehyde.
q 2005 Elsevier Ltd. All rights reserved.
1. Introduction
2. Results and discussion
Thioaurones constitute a relatively unexplored class of
compounds. More than 50 years ago they were intensively
studied as thioindigo-like dyes, and next as photochromic
compounds.1 Lately, they attracted some attention as
photoswitchable molecules2–4 and their chemistry was
recently reviewed.1 The most important method of
preparation of the compounds is the condensation of
1-benzothiophene-3-ones with benzaldehydes,5 although
several other methods are also available.1
Continuing our work on thio analogs of flavonoids of
biological interest bearing p-hydroquinone functionality,6,7
we now find that 4,7-dihydroxythioaurone derivatives can
be prepared in one step from 4-acetyl-5-alkoxy-1,3-
benzoxathiol-2-ones (1–3) and aromatic aldehydes
(Scheme 1).
The reaction provided a convenient access to a broad range
of 4,7-dihydroxythioaurone derivatives, as listed in Table 1.
Scheme 1. Formation of thioaurones 4–23.
Keywords: Thioaurones; Synthesis of; Structure of; Domino reaction.
*
Corresponding author. Tel.: C48 58 349 3148; fax: C48 58 349 3206; e-mail: markon@amg.gda.pl
0040–4020/$ - see front matter q 2005 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2005.06.107

M. T. Konieczny et al. / Tetrahedron 61 (2005) 8648–8655
Table 1. Thioaurones prepared according to Scheme 1
8649
essential. However, the reaction should be run under
anhydrous conditions to prevent hydrolysis of the carba-
moyl group at the position 7 of the product. If present in
larger amount, the product of hydrolysis (e.g., 6) can only
with difficulty be removed by crystallization and had to be
separated by low temperature extraction with dilute sodium
hydroxide or chromatography.
Compound no.
Yield (%)
Substituents
30,4,40-triOCH3
4
62
21
8
4-OCH3; 30,40-diOH
4-OCH3; 30,40-diOH; 7-OH
4-OCH3; 40-Br
5
6a
7
29
51
19
57
29
58
27
48
36
42
30
52
55
10
29
35
42
8
9
4-OCH3;
4-OCH3; pyridinyl-4 ring
20,30,4-triOCH3
10
11
12
13
14
15
16
17
18
19
20
21
22
23
The mechanism of the reaction is still tentative but a few
details are already clarified. Formation of thioaurone from
compound 1 has to involve an oxidation step, and air or
DMSO appeared as the two possible oxidants. In a related
experiment, the reaction flask was flushed with a slow
stream of argon and the gases were bubbled through a
solution of methyl iodide in acetone, resulting in precipi-
tation of a colorless solid, which was identified by IR as
trimethylsulfonium iodide (yield 29 and 48% in relation to
the isolated thioaurone; the experiment was not intended to
be quantitatively valid, and probably more dimethyl sulfide
was formed in the reaction). The result proved that DMSO
indeed acted as the oxidant. However, reaction of the
compound 1 with 3,4-dimethoxybenzaldehyde and piper-
idine run in methanol instead of DMSO also resulted in
formation of thioaurone 4, but the reaction time was longer,
the yield of the product was lower (10% in comparison to
57% in DMSO), and the thioaurone 4 was accompanied by a
complicated mixture of other compounds. One of them was
isolated, and identified as 8-hydroxy-30,40,5-trimethoxythio-
flavanone (24) (yield 9%) (Fig. 2). The result suggests that
oxidation with DMSO was advantageous but not necessary.
4,40-diOCH3
4-OCH3; 40-OH
4-OCH3; 30-OH
30,4-diOCH3; 40-OH
4-OCH3; 40-Cl
4-OCH3; 30-Cl
4-OCH3; 20-Cl
4,50-diOCH3; 30-Br; 40-OH
4-OCH3; 40-N(CH3)2
4-OCH3; 40-NO2
4,40,50-triOCH3; 30-Br
4-OCH2CH2N(C2H5)2; 30-Cl
4-OCH2CH]CH2; 30-Cl
a Formed by hydrolysis of compound 5. Traces of analogous 7-hydroxy
derivatives were present in crude products of all reactions.
The structures of the compounds were proved by elemental
analyses, IR and NMR spectra. The NMR gHMBC
spectrum of compound 4 revealed long range couplings of
the exocyclic hydrogen a with carbons 20 and 60, which
confirmed the aurone structure. For the alternative flavone
structure, such coupling seems to be improbable (Fig. 1).
Figure 1. Comparison of thioaurone and thioflavone structures.
Figure 2. Compound 24.
Measurement of coupling constants between the carbonyl
carbon (carbon 3) and a-proton gave value JZ5–6 Hz,
which proved that the carbonyl group and the a-proton are
located cis, as for the trans isomer the value of the coupling
constant should be much larger (JZ12–15 Hz).8,9 The result
is in agreement with previous observations that Z isomers of
thioaurones are thermodynamically more stable than the E
isomers, which can be prepared by irradiation of the Z form
with UV–vis light.1–4,10 The applied method of determin-
ation of double bond geometry seems to be more reliable
than the earlier methods, based on chemical shift of the
a-proton2,10 or UV spectra.2,3,11
We speculated that formation of thioaurones goes via
benzothiophen 25. To check if compound 25 is indeed
formed as an intermediate, reaction of benzoxathiol-2-one
(1) with piperidine acetate in DMSO was run in the absence
of benzaldehyde, but instead of the expected product 25,
disulfide 26 and spiro compound 27 were isolated in the
ratio 1:4, respectively, (Scheme 2). Prolongation of the time
of the reaction lead exclusively to 27. The structure of the
unusual spiro compound 27 was proved based on MS, IR
and NMR ROESY, gHMBC, and gHSQC spectra. The
NMR data demonstrated that the compound 27 existed as a
mixture of two diastereoisomers.
The described reaction seems to be general and takes place
with a variety of benzaldehydes (Table 1). The piperidine
acetate used as a catalyst and co-reactant could be replaced
by the free amine or other amine acetates, including
ammonium acetate. However, use of the piperidine acetate
resulted in well crystallizing derivatives and for this reason
all syntheses were performed with this particular salt, as
ultimately we were interested in compounds with free
hydroxy groups and the structure of the amine was not of
primary importance for us. In most cases, the reactions were
performed under argon but the inert atmosphere was not
Formation of the disulfide suggested, that this can be the
sought after intermediate, as similar formation of thiaurones
from disulfides was already reported by Samogyi.12 Indeed,
under the reaction conditions the disulfide 26 reacts cleanly
with 3,4-dimethoxybenzaldehyde to give thioaurone 4
(Scheme 3).
The prepared compounds and their derivatives were tested
as potential antitumor agents, the results will be published
elsewhere.

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M. T. Konieczny et al. / Tetrahedron 61 (2005) 8648–8655
Scheme 2. Formation of disulfide 26 and the spiro compound 27.
Scheme 3. Transformation of disulfide 26 into thioaurone.
3. Conclusion
Merck 0.2 mm silica gel 60 F254 aluminum plates.
Commercially available chemicals were reagent grade,
and DMSO was dried (Al2O3), distilled and stored over
molecular sieves.
The described, one pot reaction provides a convenient
access to 4,7-dihydroxy derivatives of thioaurones. It can
be expected, that the reaction can be extended to other
4-acetyl-1,3-benzoxathiol-2-ones, and that preparatively
useful synthesis of thioaurones, starting from
2-acetylthiophenoles or related disulfides and benzalde-
hydes in DMSO, should be possible. The presented, NMR
methods of elucidation of structures of thioaurones seem to
be superior to the previous ones, and applicable to aurones.
4.1.1. 4-Acetyl-5-methoxy-1,3-benzoxathiol-2-one (1). 4-
Acetyl-5-hydroxy-1,3-benzoxathiol-2-one13 (11.62 g,
0.055 mol), iodomethane (14 mL, 0.22 mol), dry potassium
carbonate (20 g, 0.15 mol) in anhydrous acetone (150 mL)
were refluxed, with stirring for 3 h. Water (300 mL) was
added to the cooled mixture, and the precipitated solid
was filtered off and washed with water. The wet product was
dissolved in hot acetone, decolorized with charcoal, and
precipitated by addition of water, to give 9.1 g (73%) of
4-acetyl-5-methoxy-1,3-benzoxathiol-2-one (1) as brightly
yellow crystals, mp 140–142 8C. Anal. Calcd for
C10H8O4S1: C, 53.57; H, 3.60; S, 14.27. Found: C, 53.40;
H, 3.43; S, 14.17. IR (KBr, cmK1): 1745, 1650, 1592, 1467,
1276, 1059. NMR (200 MHz, CDCl3): d 7.40 (d, 1H, JZ
9 Hz, H-7), 6.96 (d, 1H, JZ9 Hz, H-6), 4.00 (s, 3H, OCH3),
2.73 (s, 3H, COCH3).
4. Experimental
4.1. General
Melting points are uncorrected. Infrared spectra were
obtained from KBr pellets on Thermo Mattson Satellite
instrument. The 1H and 13C NMR spectra were recorded on
200 MHz (Varian Gemini) or 500 MHz (Varian Unity Plus)
spectrometers. Elemental analyses were performed on
Carlo-Erba 1108 instrument. MALDI TOF mass spectra
were obtained with a Bruker Biflex III instrument. Flash
column chromatography was performed on silica gel
(Merck, less than 230 mesh). TLC was carried out on
4.1.2. 4-Acetyl-5-[20-(N,N-diethylamino)ethoxy]-1,3-
benzoxathiol-2-one (2). 4-Acetyl-5-hydroxy-1,3-benzo-
xathiol-2-one (2.11 g, 0.01 mol), 2-chlorotriethylamine
hydrochloride (3.44 g, 0.02 mol), dry potassium carbonate

M. T. Konieczny et al. / Tetrahedron 61 (2005) 8648–8655
8651
(8.3 g, 0.06 mol) in anhydrous DMF (20 mL) were stirred at
room temperature for 1.5 h. Water and ice were added to the
cooled mixture, and the precipitated solid was filtered off
and washed with water to give 2.4 g (79%) of crude product.
Crystallization from methanol gave 1.93 g (62%) of
4-acetyl-5-[20-(N,N-diethylamino)ethoxy]-1,3-benzoxathiol-
2-one (2) as a gray solid, mp 98–99 8C. Anal. Calcd for
C15H19N1O4S1: C, 58.23; H, 6.19; N, 4.53; S, 10.34. Found:
C, 58.18; H, 6.21; N, 4.52; S, 10.38. IR (KBr, cmK1): 1744,
1662, 1594, 1460, 1274, 1051. NMR (500 MHz, DMSO): d
7.72 (d, 1H, JZ9 Hz, H-7), 7.31 (d, 1H, JZ9 Hz, H-6), 4.23
(t, 2H, JZ6 Hz, OCH2), 2.85 (t, 2H, JZ6 Hz, NCH2), 2.72
(s, 3H, COCH3), 2.54 (q, 4H, JZ7 Hz, 2!CH2CH3), 0.95
(t, 6H, JZ7 Hz, 2!CH2CH3).
Reaction of (1) with 3,4-dihydroxybenzaldehyde. The
products were precipitated by addition of cold water,
filtered, dried and separated on silica gel column in
chloroform–methanol 20:1 solution to give 5, (21%) as a
yellow solid, mp 255–260 8C dec. Anal. Calcd for
C22H21O6S1N1: C, 61.81; H, 4.95; N, 3.28; S, 7.50.
Found: C, 61.90; H, 5.14; N, 3.03; S, 7.61. IR (KBr, cmK1):
1701, 1664, 1567, 1430, 1229, 1039. NMR (200 MHz,
acetone): d 8.5 (br s, 1H, OH), 8.4 (br s, 1H, OH), 7.70 (s,
1H, H-a), 7.43 (d, 1H, JZ8.9 Hz, H-6), 7.29 (d, 1H, JZ
2.1 Hz, H-20), 7.20 (dd, 1H, J1Z8.7 Hz, J2Z2.1 Hz, H-60),
6.97 (m, 2H, H-50, H-5), 3.96 (s, 3H, OCH3), 3.70 (br s, 2H,
piperidine), 3.51 (br s, 2H, piperidine), 1.71 (br s, 6H,
piperidine), and 6, (8%) as a brick-red solid, mp 174–
178 8C. Anal. Calcd for C16H12O5S1: C, 60.75; H, 3.82; S,
10.14. Found: C, 60.57; H, 3.99; S, 10.02. IR (KBr, cmK1):
3394, 1545, 1508, 1233, 1040. NMR (200 MHz, DMSO): d
10.1 (br s, 1H, OH), 9.8 (br s, 1H, OH), 9.5 (br 0s, 1H, OH),
7.57 (s, 1H, H-a), 7.26 (d, 1H, JZ2.1 Hz, H-2 ), 7.12 (dd,
1H, J1Z2.1 Hz, J2Z8.4 Hz, H-60), 7.05 (d, 1H, JZ8.7 Hz,
H-6), 6.87 (d, 1H, JZ8.1 Hz, H-50), 6.78 (d, 1H, JZ8.8 Hz,
H-5), 3.80 (s, 3H, OCH3).
4.1.3. 4-Acetyl-5-allyloxy-1,3-benzoxathiol-2-one (3). 4-
Acetyl-5-hydroxy-1,3-benzoxathiol-2-one (2.11 g, 0.01 mol),
allyl bromide (1.73 mL, 0.02 mol), dry potassium carbonate
(4.15 g, 0.03 mol) in anhydrous DMF (20 mL) were stirred
at room temperature for 1.5 h. Water and ice were added to
the cooled mixture, and the precipitated solid was filtered
off and washed with water to give 2.3 g (92%) of crude
product. Crystallization from toluene–cyclohexane gave
1.8 g (73%) of 4-acetyl-5-allyloxy-1,3-benzoxathiol-2-one
(3) as a gray solid, mp 120–123 8C. Anal. Calcd for
C12H10O4S1: C, 57.59; H, 4.03; S, 12.79. Found: C, 57.38;
H, 3.99; S, 12.85. IR (KBr, cmK1): 1740, 1656, 1593, 1466,
1421, 1270, 1049. NMR (500 MHz, DMSO): d 7.73 (d, 1H,
JZ9 Hz, H-7), 7.28 (d, 1H, JZ9 Hz, H-6), 6.15 (m, 1H,
]CH–), 5.49 (d, 1H, JZ17 Hz, H2C]), 5.34 (d, 1H, JZ
11 Hz, H2C]), 4.80 (d, 2H, JZ5 Hz, OCH2), 2.69 (s, 3H,
COCH3).
4.2.3. 2-(40-Bromobenzylidene)-4-methoxy-7-piperidino-
carbonyloxy-2,3-dihydro-benzo[b]thiophen-3-one (7).
Reaction of (1) with 4-bromobenzaldehyde. The product
precipitated after cooling. The suspension was diluted with
methanol and filtered. The crude product was crystallized
from 2-methoxyethanol to give 7, (29%) as a yellow solid,
mp 185–188 8C. Anal. Calcd for C22H20O4S1N1Br1: C,
55.70; H, 4.25; N, 2.95; S, 6.76. Found: C, 55.42; H, 4.20;
N, 2.82; S, 6.50. IR (KBr, cmK1): 1710, 1683, 1487, 1417,
1219, 1034. NMR (500 MHz, DMSO): d 7.77 (s, 1H, H-a),
7.76 (d, 2H, Ar0), 7.69 (d, 2H, JZ8.3 Hz, Ar0), 7.53 (d, 1H,
JZ8.8 Hz, H-6), 7.01 (d, 1H, JZ9.3 Hz, H-5), 3.93 (s, 3H,
OCH3), 3.62 (br s, 2H, piperidine), 3.42 (br s, 2H, piperi-
dine), 1.64 (br s, 4H, piperidine), 1.56 (br s, 2H, piperidine).
4.2. General procedure for reaction of 4-acetyl-1,3-
benzoxathiol-2-ones (1–3) with benzaldehydes
4-Acetyl-1,3-benzoxathiol-2-ones (1–3) (4 mmol), a benz-
aldehyde (6 mmol), piperidine acetate (870 mg, 6 mmol) in
anhydrous DMSO (4 mL) were heated at 100–110 8C, with
stirring for 1–2 h. The reaction mixture was cooled down
and elaborated as described for particular benzaldehydes.
4.2.4. 2-Benzylidene-4-methoxy-7-piperidinocarbonyl-
oxy-2,3-dihydro-benzo[b]thiophen-3-one (8). Reaction
of (1) with benzaldehyde. The product precipitated after
cooling. The suspension was diluted with methanol and
filtered. The crude product was purified on silica gel column
in chloroform to give 8, (51%) as a yellow solid, mp 180–
181 8C. Anal. Calcd for C22H21O4S1N1: C, 66.82; H, 5.35;
N, 3.54; S, 8.11. Found: C, 66.99; H, 5.51; N, 3.76; S, 8.34.
IR (KBr, cmK1): 1715, 1681, 1585, 1492, 1425, 1220, 1031,
NMR (200 MHz, DMSO): d 7.81 (s, 1H, H-a), 7.42–7.80
(m, 6H, Ar0, H-6), 7.00 (d, 1H, JZ9.0 Hz, H-5), 3.93 (s, 3H,
OCH3), 3.62 (br s, 2H, piperidine), 3.44 (br s, 2H,
piperidine), 1.64 (br s, 6H, piperidine).
4.2.1. 2-(30,40-Dimethoxybenzylidene)-4-methoxy-7-
piperidinocarbonyloxy-2,3-dihydro-benzo[b]thiophen-
3-one (4). Reaction of 1 with 3,4-dimethoxybenzaldehyde.
The product precipitated after cooling. The suspension
was diluted with methanol and filtered. The yellow solid
was washed with methanol, and crystallized from
2-methoxyethanol to give 4, (62%) as yellow solid, mp
173–175 8C. Anal. Calcd for C24H25O6S1N1: C, 63.28; H,
5.53; N, 3.07; S, 7.04. Found: C, 63.39; H, 5.38; N, 3.15; S,
6.87. IR (KBr, cmK1): 1720, 1662, 1584, 1509, 1223, 1040.
NMR (200 MHz, CDCl3): d 7.91 (s, 1H, H-a), 7.35–7.50
(m, 2H, H-6, H-60), 7.3 (br s, 1H, H-20), 7.05 (d, 1H, JZ
8.4 Hz, H-50), 6.82 (d, 1H, JZ8.9 Hz, H-5), 4.07 (s, 3H,
OCH3), 4.04 (s, 3H, OCH3), 4.03 (s, 3H, OCH3), 3.75 (br s,
2H, piperidine), 3.60 (br s, 2H, piperidine), 1.77 (br s, 6H,
piperidine).
4.2.5. 2-[(Pyridin-4yl)-methylene]-4-methoxy-7-piperi-
dinocarbonyloxy-2,3-dihydro-benzo[b]thiophen-3-one
(9). Reaction of (1) with 4-pyridinecarboxaldehyde. Water
was added to the cooled reaction mixture, the precipitated
oil was dissolved in methylene chloride, the solution was
washed with water, dried and evaporated to dryness. The
residue was purified on silica gel column in methylene
chloride–ethyl acetate 3:1 solution to give 30%, and after
crystallization from 2-methoxyethanol 19% of 9 as a yellow
solid, mp 203–205 8C. Anal. Calcd for C21H20N2O4S1: C,
63.62; H, 5.08; N, 7.07; S, 8.09. Found: C, 63.47; H, 5.20;
4.2.2. 2-(30,40-Dihydroxybenzylidene)-4-methoxy-7-
piperidinocarbonyloxy-2,3-dihydro-benzo[b]thiophen-
3-one (5) and 2-(30,40-dihydroxybenzylidene)-7-hydroxy-
4-methoxy-2,3-dihydro-benzo[b]thiophen-3-one (6).

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M. T. Konieczny et al. / Tetrahedron 61 (2005) 8648–8655
N, 7.28; S, 8.37. IR (KBr, cmK1): 1720, 1978, 1583, 1427,
1226, 1034. NMR (200 MHz, CDCl3): d 8.73 (d, 2H, JZ
4 Hz, H-20,H-60), 7.73 (s, 1H, H-a), 7.56 (d, 2H, JZ6 Hz,
H-30, H-50), 7.41 (d, 1H, JZ8.9 Hz, H-6), 6.77 (d, 1H, JZ
8.9 Hz, H-5), 4.01 (s, 3H, OCH3), 3.69 (br s, 2H,
piperidine), 3.55 (br s, 2H, piperidine), 1.71 (br s, 6H,
piperidine).
was added to the cooled reaction mixture, the precipitated
oil was washed with water, dissolved in chloroform, the
solution was washed with water, dried [(Na)2SO4] and
evaporated to dryness. The residue was crystallized from
2-methoxyethanol and washed with methanol to give 13,
(27%) as a yellow solid, mp 255–258 8C. Anal. Calcd for
C22H21N1O5S1: C, 64.22; H, 5.14; N, 3.40; S, 7.79. Found:
C, 64.47; H, 5.11; N, 3.23; S, 7.54. IR (KBr, cmK1): 3322,
1711, 1670, 1578, 1489, 1227, 1042, NMR (200 MHz,
DMSO): d 9.86 (br s, 1H, OH), 7.70 (s, 1H, H-a), 7.50 (d,
1H, JZ8.9 Hz, H-6), 7.32 (t, 1H, JZ7.7 Hz, H-50), 7.16 (m,
2H, H-20, H-60),06.99 (d, 1H, JZ9. 0 Hz, H-5), 6.88 (dd, 1H,
JZ7.8 Hz, H-4 ), 3.92 (s, 3H, OCH3), 3.53 (br s, 2H,
piperidine), 3.43 (br s, 2H, piperidine), 1.63 (br s, 6H,
piperidine).
4.2.6. 2-(20,30-Dimethoxybenzylidene)-4-methoxy-7-
piperidinocarbonyloxy-2,3-dihydro-benzo[b]thiophen-
3-one (10). Reaction of (1) with 2,3-dimethoxybenzalde-
hyde. The product precipitated after cooling. The suspen-
sion was diluted with methanol and filtered. The yellow
solid was crystallized from 2-methoxyethanol to give 10
(57%) as a yellow solid, mp 166–167 8C. Anal. Calcd for
C24H25N1O6S1: C, 63.28; H, 5.53; N, 3.07; S, 7.04. Found:
C, 63.10; H, 5.58; N, 3.00; S, 7.17. IR (KBr, cmK1): 1724,
1681, 1582, 1488, 1425, 1224, 1084, 1034. NMR
(200 MHz, DMSO): d 8.00 (s, 1H, H-a), 7.51 (d, 1H, JZ
8.9 Hz, H-6), 7.18–7.30 (m, 3H, Ar0), 7.00 (d, 1H, JZ
8.9 Hz, H-5), 3.93 (s, 3H, OCH3), 3.86 (s, 3H, OCH3), 3.80
(s, 3H, OCH3), 3.62 (br s, 2H, piperidine), 3.42 (br s, 2H,
piperidine), 1.62 (br s, 6H, piperidine).
4.2.10. 2-(40-Hydroxy-30-methoxybenzylidene)-4-meth-
oxy-7-piperidinocarbonyloxy-2,3-dihydro-benzo[b]thio-
phen-3-one (14). Reaction of (1) with 4-hydroxy-3-
methoxybenzaldehyde. The product precipitated after
cooling and addition of methanol. The suspension was
filtered, the yellow solid was washed with methanol, crys-
tallized twice from 2-methoxyethanol and washed with
methanol to give 14, (48%) as an orange solid, mp 195–
196 8C. Anal. Calcd for C23H23N1O6S1: C, 62.57; H, 5.25;
N, 3.17; S, 7.26. Found: C, 62.78; H, 5.39; N, 3.33; S, 7.02.
IR (KBr, cmK1): 3324, 1700, 1670, 1570, 1512, 1428, 1232,
1038. NMR (200 MHz, DMSO): d 10.00 (br s, 1H, OH),
7.74 (s, 1H, H-a), 7.48 (d, 1H, JZ8.8 Hz, H-6), 7.33 (d, 1H,
JZ2.0 Hz, H-20), 7.26 (dd, 1H, J1Z8.2 Hz, J2Z2.0 Hz, H-
600), 6.97 (d, 1H, JZ8.9 Hz, H-5), 6.94 (d, 1H, JZ8.2 Hz, H-
5 ), 3.91 (s, 3H, OCH3), 3.85 (s, 3H, OCH3), 3.62 (br s, 2H,
piperidine), 3.43 (br s, 2H, piperidine), 1.63 (br s, 6H,
piperidine).
4.2.7. 2-(40-Methoxybenzylidene)-4-methoxy-7-piperi-
dinocarbonyloxy-2,3-dihydro-benzo[b]thiophen-3-one
(11). Reaction of (1) with 4-methoxybenzaldehyde. Water
was added to the cooled reaction mixture, the precipitated
oil was washed with water, dissolved in chloroform, the
solution was washed with water, dried and evaporated to
dryness. The residue was purified on silica gel column in
chloroform–toluene 3:1 solution and crystallized from
2-methoxyethanol to give 29% of 11 as a yellow solid,
mp 156–157 8C. Anal. Calcd for C23H23N1O5S1: C, 64.92;
H, 5.45, N, 3.29; S, 7.54. Found: C, 64.67; H, 5.33; N, 3.11;
S, 7.31. IR (KBr, cmK1): 1727, 1673, 1571, 1509, 1426,
1225, 1176, 1029. NMR (200 MHz, DMSO): d 7.77 (s, 1H,
H-a), 7.72 (d, 2H, JZ8.8 Hz, H-20, H-60), 07.49 (0d, 1H, JZ
8.9 Hz, H-6), 7.12 (d, 2H, JZ8.7 Hz, H-3 , H-5 ), 6.98 (d,
1H, JZ9.0 Hz, H-5), 3.91 (s, 3H, OCH3), 3.84 (s, 3H,
OCH3), 3.62 (br s, 2H, piperidine), 3.44 (br s, 2H,
piperidine), 1.64 (br s, 6H, piperidine).
4.2.11. 2-(40-Chlorobenzylidene)-4-methoxy-7-piperi-
dinocarbonyloxy-2,3-dihydro-benzo[b]thiophen-3-one
(15). Reaction of (1) with 4-chlorobenzaldehyde. The pro-
duct precipitated after cooling. The suspension was diluted
with methanol and filtered. The yellow solid was washed
with methanol and dried to give 44% of crude product. The
product was purified on silica gel column in chloroform to
give 15, (36%) as a yellow solid, mp 189–190 8C. Anal.
Calcd for C22H20N1O4S1Cl1: C, 61.46; H, 4.69; N, 3.26; S,
7.46. Found: C, 61.27; H, 4.81; N, 3.13; S, 7.21. IR (KBr,
cmK1): 1714, 1681, 1582, 1492, 1425, 1221, 1027. NMR
(500 MHz, DMSO): d 7.79 (s, 1H, H-a), 7.76 (d, 2H, JZ
8.3 Hz, H-20, H-60), 7.63 (d, 2H, JZ8.3 Hz, H-30, H-50),
7.53 (d, 1H, JZ8.9 Hz, H-6), 7.01 (d, 1H, JZ8.9 Hz, H-5),
3.93 (s, 3H, OCH3), 3.62 (br s, 2H, piperidine), 3.43 (br s,
2H, piperidine), 1.64 (br s, 4H, piperidine), 1.56 (br s, 2H,
piperidine).
4.2.8. 2-(40-Hydroxybenzylidene)-4-methoxy-7-piperi-
dinocarbonyloxy-2,3-dihydro-benzo[b]thiophen-3-one
(12). Reaction of (1) with 4-hydroxybenzaldehyde. The
product precipitated after cooling. The suspension was
diluted with methanol and filtered. The yellow solid was
washed with methanol, crystallized from 2-methoxyethanol
and washed with methanol to give 12, (58%) as a yellow
solid, mp 238–240 8C. Anal. Calcd for C22H21N1O5S1: C,
64.22; H, 5.14; N, 3.40; S, 7.79. Found: C, 64.11; H, 5.00;
N, 3.27; S, 7.53. IR (KBr, cmK1): 3205, 1719, 1659, 1561,
1512, 1426, 1226, 1173, 1040. NMR (200 MHz, DMSO): d
10.35 (br s,01H, OH), 7.72 (s, 1H, H-a), 7.62 (d, 2H, JZ
8.6 Hz, H-2 , H-60), 7.47 (d, 1H, JZ8.9 Hz, H-6), 06.96 (0d,
1H, JZ8.9 Hz, H-5), 6.94 (d, 2H, JZ8.7 Hz, H-3 , H-5 ),
3.91 (s, 3H, OCH3), 3.62 (br s, 2H, piperidine), 3.54 (br s,
2H, piperidine), 1.63 (br s, 6H, piperidine).
4.2.12. 2-(30-Chlorobenzylidene)-4-methoxy-7-piperi-
dinocarbonyloxy-2,3-dihydro-benzo[b]thiophen-3-one
(16). Reaction of (1) with 3-chlorobenzaldehyde. The
product precipitated after cooling. The suspension was
diluted with methanol and filtered. The yellow solid was
washed with methanol, crystallized from 2-methoxyethanol
and washed with methanol to give 16, (42%) as a yellow
solid, mp 170–172 8C. Anal. Calcd for C22H20N1O4S1Cl1:
C, 61.46; H, 4.69; N, 3.26; S, 7.46. Found: C, 61.25; H, 4.45;
N, 3.08; S, 7.67. IR (KBr, cmK1): 1714, 1683, 1582, 1490,
4.2.9. 2-(30-Hydroxybenzylidene)-4-methoxy-7-piperi-
dinocarbonyloxy-2,3-dihydro-benzo[b]thiophen-3-one
(13). Reaction of (1) with 3-hydroxybenzaldehyde. Water

M. T. Konieczny et al. / Tetrahedron 61 (2005) 8648–8655
8653
1425, 1222, 1026. NMR (500 MHz, DMSO): d 7.81 0(s, 1H,
H-20), 7.79 (s, 1H, H-a), 7.71 (d, 1H, JZ7.8 Hz, H-2 ), 7.59
(t, 1H, JZ7.8 Hz, H-50), 7. 55–7.57 (m, 2H, H-40, H-6), 7.02
(d, 1H, JZ8.9 Hz, H-5), 3.93 (s, 3H, OCH3), 3.62 (br s, 2H,
piperidine), 3.43 (br s, 2H, piperidine), 1.65 (br s, 4H,
piperidine), 1.56 (br s, 2H, piperidine).
4.2.16. 2-(40-Nitrobenzylidene)-4-methoxy-7-piperidino-
carbonyloxy-2,3-dihydro-benzo[b]thiophen-3-one (20).
Reaction of (1) with 4-nitrobenzaldehyde. The product
precipitated after cooling. The suspension was diluted with
methanol and filtered. The yellow solid was washed with
methanol, purified on silica gel column in chloroform,
crystallized from 2-methoxyethanol and washed with
methanol to give 20, (10%) as a yellow solid, mp 242–
244 8C. Anal. Calcd for C22H20N2O6S1: C, 59.99; H, 4.58;
N, 6.36; S, 7.28. Found: C, 60.23; H, 4.41; N, 6.53; S, 7.07.
IR (KBr, cmK1): 1715, 1688, 1582, 1512, 1490, 1427, 1339,
1226, 1031.0NMR0 (200 MHz, DMSO): d 8.37 (d, 2H, JZ
8.7 Hz, H-2 , H-6 ), 7.99 (d, 2H, JZ8.7 Hz, H-30, H-50),
7.88 (s, 1H, H-a), 7.56 (d, 1H, JZ8.9 Hz, H-6), 7.04 (d, 1H,
JZ8.9 Hz, H-5), 3.94 (s, 3H, OCH3), 3.62 (br s, 2H,
piperidine), 3.46 (br s, 2H, piperidine), 1.64 (br s, 6H,
piperidine).
4.2.13. 2-(20-Chlorobenzylidene)-4-methoxy-7-piperi-
dinocarbonyloxy-2,3-dihydro-benzo[b]thiophen-3-one
(17). Reaction of (1) with 2-chlorobenzaldehyde. Water was
added to the cooled reaction mixture, the precipitated oil
was washed with water, dissolved in chloroform, the solu-
tion was washed with water, dried (MgSO4) and evaporated
to dryness. The residue was purified on silica gel column in
chloroform–toluene 3:1 solution to give 30% of 17 as a
yellow solid, mp 170 171 8C. Anal. Calcd for C22H20N1O4-
S1Cl1: C, 61.46; H, 4.69; N, 3.26; S, 7.46. Found: C, 61.68;
H, 4.62; N, 3.39; S, 7.24. IR (KBr, cmK1): 1722, 1681,
1582, 1490, 1424, 1218, 1145, 1030. NMR (200 MHz,
DMSO): d 7.99 (s, 1H, H-a), 7.79 (dd, 1H, J1Z7.2 Hz, J2Z
1.9 Hz, H-60), 7.44–7.70 (m, 4H, H-6, H-30, H-40, H-50),
7.02 (d, 1H, JZ9.1 Hz, H-5), 3.93 (s, 3H, OCH3), 3.59 (br s,
2H, piperidine), 3.42 (br s, 2H, piperidine), 1.61 (br s, 6H,
piperidine).
4.2.17. 2-(30-Bromo-40,50-dimethoxybenzylidene)-4-
methoxy-7-piperidinocarbonyloxy-2,3-dihydro-benzo[b]
thiophen-3-one (21). Reaction of (1) with 3-bromo-4,5-
dimethoxybenzaldehyde. The product precipitated after
cooling. The suspension was diluted with methanol and
filtered. The crude product was purified on silica gel column
in chloroform–ethyl acetate 100:1 solution and crystallized
from chloroform–methanol mixture to give 21, (29%) a
yellow solid, mp 194–196 8C. Anal. Calcd for C24H24N1-
O6S1Br1: C, 53.94; H, 4.53; N, 2.62; S, 6.00. Found: C,
53.90; H, 4.40; N, 2.54; S, 5.85. IR (KBr, cmK1): 1716,
1675, 1582, 1489, 1428, 1229, 1039. NMR (200 MHz,
DMSO): d 7.73 (s, 1H, H-a), 7.55 (d, 1H, JZ1.8 Hz, H-200),
7.51 (d, 1H, JZ9.0 Hz, H-6), 7.44 (d, 1H, JZ1.9, H-6 ),
6.99 (d, 1H, JZ9.0 Hz, H-5), 3.92 (s, 3H, OCH3), 3.90 (s,
3H, OCH3), 3.81 (s, 3H, OCH3), 3.61 (br s, 2H, piperidine),
3.45 (br s, 2H, piperidine), 1.64 (br s, 6H, piperidine).
4.2.14. 2-(30-Bromo-40-hydroxy-50-methoxybenzyli-
dene)-4-methoxy-7-piperidinocarbonyloxy-2,3-dihydro-
benzo[b]thiophen-3-one (18). Reaction of (1) with
3-bromo-4-hydroxy-5-methoxybenzaldehyde. The product
precipitated after cooling. The suspension was diluted with
methanol and filtered. The yellow solid was washed with
methanol, crystallized from 2-methoxyethanol and washed
with methanol to give 18, (52%) as a yellow solid, mp 227–
229 8C. Anal. Calcd for C23H22N1O6S1Br1: C, 53.08; H,
4.26; N, 2.69; S, 6.16. Found: C, 52.87; H, 4.45; N, 2.41; S,
6.00. IR (KBr, cmK1): 3388, 1715, 1667, 1579, 1500, 1427,
1226, 1038. NMR (500 MHz, DMSO): d 10.46 (br0 s, 1H,
OH), 7.73 (s, 1H, H-a), 7.55 (d, 1H, JZ1.9 Hz, H-20), 7.51
(d, 1H, JZ8.8 Hz, H-6), 7.39 (d, 1H, JZsmall, H-6 ), 7.00
(d, 1H, JZ9.3 Hz, H-5), 3.92 (s, 3H, OCH3), 3.91 (s, 3H,
OCH3), 3.62 (br s, 2H, piperidine), 3.44 (br s, 2H,
piperidine), 1.66 (br s, 4H, piperidine), 1.56 (br s, 2H,
piperidine).
4.2.18. 2-(30-Chlorobenzylidene)-4-[200-(N,N-diethyl-
amino)ethoxy]-7-piperidinocarbonyloxy-2,3-dihydro-
benzo[b]thiophen-3-one (22). Reaction of (2) with
3-chlorobenzaldehyde. The reaction mixture was poured
into solution of potassium carbonate (2 g) in water (80 mL)
to give a dark oil. Water was decanted and the oil was
washed several time with water to remove DMSO. The
residue was dissolved in ethyl acetate, washed with water,
dried (sodium sulfate) and evaporated. The residue was
purified on silica gel column in chloroform–methanol 10:1
solution and crystallized from methanol to give 22, (35%) as
a yellow solid, mp 122–123 8C. Anal. Calcd for C27H31N2-
O4S1Cl1: C, 62.96; H, 6.07; N, 5.44; S, 6.23. Found: C,
62.86; H, 5.91; N, 5.45; S, 6.16. IR (KBr, cmK1): 1721,
1682, 1580, 1426, 1223, 1035. NMR (500 MHz, DMSO): d
7.79 (br s, 2H, H-a, H-20), 7.70 (d, 1H, JZ7.8 Hz, H-600),
7.59 (t, 1H, JZ7.8 Hz, H-50), 7.54 (d, 1H, JZ7.8 Hz, H-4 ),
7.50 (d, 1H, JZ9.3 Hz, H-6), 7.02 (d, 1H, JZ9.3 Hz, H-5),
4.19 (t, 2H, JZ4.9 Hz, OCH2), 3.62 (br s, 2H, piperidine),
3.43 (br s, 2H, piperidine), 2.84 (t, 2H, JZ5.4 Hz, NCH2),
2.60 (q, 4H, JZ7.0 Hz, 2!CH2), 1.65 (br s, 4H,
piperidine), 1.56 (br s, 2H, piperidine), 0.99 (t, 6H, JZ
7.3 Hz, 2!CH3).
4.2.15. 2-(40-Dimethylaminobenzylidene)-4-methoxy-7-
piperidinocarbonyloxy-2,3-dihydro-benzo[b]thiophen-3-
one (19). Reaction of (1) with 4-dimethylaminobenzaldehyde.
Water was added to the cooled reaction mixture, the pre-
cipitated oil was washed with water, dissolved in chloro-
form, the solution was washed with water, dried (MgSO4)
and evaporated to dryness. The residue was washed with
methanol, crystallized twice from 2-methoxyethanol and
washed with methanol to give 19, (55%) as a red solid, mp
218–222 8C. Anal. Calcd for C24H26N2O4S1: C, 65.73; H,
5.98; N, 6.39; S, 7.31. Found: C, 65.82; H, 5.92; N, 6.30; S,
7.18. IR (KBr, cmK1): 1723, 1665, 1561, 1522, 1369, 1228,
1033. NMR (200 MHz, DMSO): d 7.70 (s, 1H, H-a), 7.60
(d, 2H, JZ9.0 Hz, H-20, H-60), 7.45 (d, 1H, JZ8.9 Hz,
H-6), 6.94 (d, 1H, JZ8.9 Hz, H-5), 6.85 (d, 2H, JZ8.9 Hz,
H-30, H-50), 3.90 (s, 3H, OCH3), 3.62 (br s, 2H, piperidine),
3.43 (br s, 2H, piperidine), 3.03 (s, 6H, N(CH3)2), 1.64 (br s,
6H, piperidine).
4.2.19. 2-(30-Chlorobenzylidene)-4-allyloxy]-7-piperi-
dinocarbonyloxy-2,3-dihydro-benzo[b]thiophen-3-one
(23). Reaction of (3) with 3-chlorobenzaldehyde. The

8654
M. T. Konieczny et al. / Tetrahedron 61 (2005) 8648–8655
product precipitated after cooling. The suspension was
diluted with methanol and filtered. The crude product was
crystallized from 2-methoxyethanol to give 23, (42%) as a
yellow solid, mp 144–146 8C. Anal. Calcd for C24H22N1-
O4S1Cl1: C, 63.22; H, 4.86; N, 3.07; S, 7.03. Found: C,
62.96; H, 4.73; N, 3.10; S, 7.13. IR (KBr, cmK1): 1721,
1679, 1580, 1424, 1221, 1011. NMR (500 MHz, DMSO): d
7.79 (s, 2H, H-a, H-20), 7.70 (d, 1H, JZ7.3 Hz, H-60), 7.59
(t, 1H, JZ7.8 Hz, H-50), 7.54 (br d, 1H, JZ8.3 Hz, H-40),
7.50 (d, 1H, JZ9.3 Hz, H-6), 7.00 (d, 1H, JZ8.8 Hz, H-5),
6.07 (m, 1H, ]CH–), 5.61 (d, 1H, JZ16.2 Hz, H2C]),
5.32 (d, 1H, JZ10.2 Hz, H2C]), 4.75 (d, 2H, JZ3.9 Hz,
OCH2), 3.62 (br s, 2H, piperidine), 3.43 (br s, 2H,
piperidine), 1.65 (br s, 4H, piperidine), 1.56 (br s, 2H,
piperidine).
Anal. Calcd for C30H34O8N2S2!H2O: MZ632.75; C,
56.95; H, 5.73; N, 4.43; S, 10.14. Found: C, 56.98; H,
5.63; N, 4.30; S, 10.13. MS MALDI TOF: 597 (MCKOH),
614 (MC), 637 (MCCNa), 653 (MCCK). IR (KBr, cmK1):
3442, 1722, 1580, 1488, 1425, 1225, 1141, 1048, 1020.
NMR (500 MHz, DMSO) (the compound exists as a mixture
of two diastereoisomers. Full NMR data, including 13C,
ROESY, gHSQC, and gHMBC spectra, are given in the
Supplementary data, the following list presents only 1H data
for the main isomer): d 7.48 (d, 1H, JZ8.8 Hz, H-6), 7.09
(d, 1H, JZ9.3 Hz, H-60), 6.88 (d, 1H, JZ7.8 Hz, H-5), 6.82
(d, 1H, JZ9.3 Hz, H-50), 6.46 (s, 1H, OH), 3.81 (s, 3H,
0
OCH3), 3.79 (s, 3H, OCH3 ), 3.34–3.60 (br m, 8H,
piperidine), 1.42–1.65 (br m, 12H, piperidine), 1.64 (s,
3H, CH3).
4.2.20. Reaction of 4-acetyl-5-methoxy-1,3-benzoxathiol-
2-one (1) with 3,4-dimethoxybenzaldehyde in methanol.
4-Acetyl-5-methoxy-1,3-benzoxathiol-2-one (1) (224 mg,
1 mmol), 3,4-dimethoxybenzaldehyde (250 mg, 1.5 mmol)
and piperidine (0.15 mL, 1.5 mmol) in methanol (2 mL)
were stirred at 60 8C for 5 h, and the solution was left for
cooling. The precipitated solid was filtered off, and washed
with methanol, to give 2-(30,40-dimethoxybenzylidene)-4-
methoxy-7-piperidinocarbonyloxy-2,3-dihydro-benzo[b]
thiophen-3-one (4) (36 mg, 8%). The combined filtrates
were evaporated and the residue was separated on silica gel
column in chloroform, to give a second fraction of 4 (10 mg,
2%), and 8-hydroxy-30,40,5-trimethoxythioflavanone (24)
(31 mg, 9%) as a yellow solid, mp 180–182 8C. Anal. Calcd
for C18H18O5S1: C, 62.41; H, 5.24; S, 9.24. Found: C, 62.19;
H, 5.30; S, 9.02. IR (KBr, cmK1): 3285, 1646, 1570, 1518,
1466, 1246, 1037. NMR (500 MHz, DMSO): d 9.76 (s, 1H,
OH), 7.07 (d, 1H, JZ2 Hz, H-20), 6.99 (dd, 1H, J1Z8.3 Hz,
J2Z1.9 Hz, H-60), 6.94 (d, 1H, JZ8.8 Hz, H-7), 6.93 (d,
1H, JZ8.3 Hz, H-50), 6.73 (d, JZ9.3 Hz, H-6), 4.65 (dd,
1H, J1Z13.1 Hz, J2Z3.0 Hz, H-2), 3.76 (s, 3H, OCH3),
3.75 (s, 3H, OCH3), 3.70 (s, 3H, OCH3), 3.32 (dd, 1H, J1Z
15.6 Hz, J2Z13.6 Hz, H-3), 2.86 (dd, 1H, J1Z15.2 Hz,
J2Z3.0 Hz, H-3).
4.2.22. Reaction of 2-acetyl-3-methoxy-6-piperi-
dinocarbonyloxyphenyl disulfide (26) with 3,4-di-
methoxybenzaldehyde.
piperidinocarbonyl-oxyphenyl disulfide (26) (11 mg,
0.028 mmol), 3,4-dimethoxybenzaldehyde (7 mg,
2-Acetyl-3-methoxy-6-
0.042 mmol) and piperidine acetate (6 mg, 0.04 mmol) in
anhydrous DMSO (0.5 mL) were stirred at 90 8C for 1 h.
The solution was cooled, the product was precipitated with
water, filtered, washed with water and methanol, to give
thioaurone 4 (4 mg).
Acknowledgements
The authors thank Taiho Pharmaceutical Company, Japan
for financial support.
Supplementary data
Supplementary data associated with this article can be
found, in the online version, at doi:10.1016/j.tet.2005.06.
107
4.2.21. Reaction of 4-acetyl-5-methoxy-1,3-benzoxathiol-
2-one (1) with piperidine acetate in DMSO. Solution of
4-acetyl-5-methoxy-1,3-benzoxathiol-2-one (1) (224 mg,
1 mmol) and piperidine acetate (218 mg, 1.5 mmol) in dry
DMSO (2 mL) was deoxygenated and stirred under argon at
60 8C for 5 h. The reaction mixture was cooled in ice, and
products were precipitated by addition of water. The crude
mixture (280 mg) was separated on silica gel column in
chloroform–ethyl acetate 3:1 solution to give 2-acetyl-3-
methoxy-6-piperidinocarbonyloxyphenyl disulfide (26)
(20 mg, 6%) as a beige solid, mp 159–161 8C. Anal.
Calcd for C30H36O8N2S2: MZ616.726; C-58.42; H-5.89;
N-4.55; S-10.38. Found: C-58.75; H, 5.98; N, 4.44; S, 10.55.
MS MALDI TOF: 639 (MCCNa), 655 (MCCK). IR (KBr,
cmK1): 1720, 1582, 1420, 1224, 1138, 1044, 1022. NMR
(500 MHz, CDCl3): d 7.21 (d, 1H, JZ9.3 Hz, H-4), 6.93 (d,
1H, JZ9.3 Hz, H-5), 3.80 (s, 3H, OCH3), 3.48 (br s, 4H,
H-piperidine), 2.16 (s, 3H, COCH3), 1.61 (br m, 6H,
H-piperidine); As the second product was0 eluted 4,400-
dimethoxy-7,70-di(piperidinocarbonyloxy)-3 -hydroxy-3 -
methyl-3-keto-[3,30-spirobi(2H,20H,3H,30H-benzo[b]thio-
phen)] (27), (150 mg, 50%) as a cream solid, mp 140–147 8C.
Table 1—NMR data of the spiro compound 27; Figure 1—
low field part of 1H NMR spectrum of 27; Figure 2—
1
high field part of H NMR spectrum of 27; Figures 3 to
7—13C NMR of 27; Figure 8—ROESY spectrum of 27;
Figure 9—gHMBC spectrum of 27; Figure 10—gHSQC
spectrum of 27.
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